Stem Cell Therapy and Regenerative Medicine

O’Brien, Timothy; Barry, Frank

doi:10.4065/84.10.859

Cited by 35 publications

(16 citation statements)

References 16 publications

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“…They provide benefit in terms of healing and regeneration but are unable to fully resolve injuries or diseases (19)(20)(21). Introducing new products to the market is made difficult by the large time and monetary investments required to earn FDA approval in this field.…”

Section: Therapies In the Marketmentioning

confidence: 99%

Regenerative medicine: Current therapies and future directions

Mao

Mooney

2015

Proc. Natl. Acad. Sci. U.S.A.

677

439

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Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. Regenerative medicine, an interdisciplinary field that applies engineering and life science principles to promote regeneration, can potentially restore diseased and injured tissues and whole organs. Since the inception of the field several decades ago, a number of regenerative medicine therapies, including those designed for wound healing and orthopedics applications, have received Food and Drug Administration (FDA) approval and are now commercially available. These therapies and other regenerative medicine approaches currently being studied in preclinical and clinical settings will be covered in this review. Specifically, developments in fabricating sophisticated grafts and tissue mimics and technologies for integrating grafts with host vasculature will be discussed. Enhancing the intrinsic regenerative capacity of the host by altering its environment, whether with cell injections or immune modulation, will be addressed, as well as methods for exploiting recently developed cell sources. Finally, we propose directions for current and future regenerative medicine therapies.regenerative medicine | tissue engineering | biomaterials | review

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Section: Therapies In the Marketmentioning

confidence: 99%

Regenerative medicine: Current therapies and future directions

Mao

Mooney

2015

Proc. Natl. Acad. Sci. U.S.A.

677

439

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“…This can be shown to be the case with photoreceptor transplants, 13 but may not be the case for other stem cells delivered to other sites in the body, with a paracrine mode of action favoured for some. [26][27][28] In this case, the premise is that secretion of hormones, growth factors and/or extracellular matrix components by the stem cells, in complex dialogue with pre-existing damaged tissue, may be stimulating transplanted cells to secrete therapeutic substances in response to the injured host tissue, thereby providing benefit. [26][27][28] The addition of pRPCs with glial potential to damaged retinas may enhance natural repair processes, by physical contact and structural repair, by providing an antiapoptotic effect (as suggested by increased Bcl2 levels), and by secretion of hormones and/or growth factors [26][27][28] or, perhaps, via increased glial protection of normally unmyelinated segments of ganglion cell axons.…”

Section: Molecular Markersmentioning

confidence: 99%

Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy

et al. 2014

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Primary mitochondrial disorders occur at a prevalence of one in 10 000; B50% of these demonstrate ocular pathology. Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder. LHON results from retinal ganglion cell pathology, which leads to optic nerve degeneration and blindness. Over 95% of cases result from one of the three common mutations in mitochondrial genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory chain. Various therapies for LHON are in development, for example, intravitreal injection of adeno-associated virus carrying either the yeast NDI1 gene or a specific subunit of mammalian Complex I have shown visual improvement in animal models. Given the course of LHON, it is likely that in many cases prompt administration may be necessary before widespread cell death. An alternative approach for therapy may be the use of stem cells to protect visual function; this has been evaluated by us in a rotenone-induced model of LHON. Freshly dissected embryonic retinal cells do not integrate into the ganglion cell layer (GCL), unlike similarly obtained photoreceptor precursors. However, cultured retinal progenitor cells can integrate in close proximity to the GCL, and act to preserve retinal function as assessed by manganese-enhanced magnetic resonance imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON therefore represent a promising therapeutic approach, and may be of particular utility in treating more advanced disease. INTRODUCTIONPrimary mitochondrial disorders (those caused by mutations in the mitochondrial genome) occur at a prevalence of B1 in 10 000, with 1 in 200 individuals carrying at-risk mutations. 1 Approximately 50% demonstrate some form of ocular pathology. 2 Mitochondria provide energy in the form of ATP generated by oxidative phosphorylation; therefore, mitochondrial mutations primarily affect tissues with the greatest energy requirements, such as the retina, the inner ear, central and peripheral nervous systems and cardiac and skeletal muscle. 2,3 Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder, with a prevalence of B1 in 31 000-50 000 in northern Europe. The prevalence of at-risk carriers is much higher, estimated at 1 in 8 500 in the UK; furthermore, primary LHON mutations were found in 1 out of 350 neonatal umbilical cord samples. 1,4 LHON is maternally inherited, often results from homoplasmy of the causative mitochondrial mutation, and is incompletely penetrant; visual loss occurs in 50% of males and 10% of females. Symptoms result from retinal ganglion cell (RGC) pathology, which leads to RGC death via apoptosis, resulting in optic nerve degeneration and subsequent blindness. Nonocular symptoms of mitochondrial dysfunction may also be present. 1,4 Although many mutations implicated in LHON have been described, 90-95% of the cases result from one of the three common mutations in mitochondrial genes including MTND1, MTND4 and MTND6, which encode elements of ...

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“…However, as it is currently, stem cell therapies (in general) and off-the-shelf products (in particular) are experiencing some difficulties. Specifically, there is no accurate description of standardization and characterization of pre-transplanted cells OBrien and Barry (2009). Indeed, researchers are still worried and cautioned about the role of MSCs in tumor formation Frese et al (2016); Sherman et al (2017).…”

Section: Introductionmentioning

confidence: 99%

Phenotypic and cytogenetic characterization of expanded adipose derived stem cells

Truong

Pham

2018

Sci. Tech. Dev. J.

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Introduction: Human adipose derived stem cells (hASCs) have great potential for regenerative medicine. The demand for hASCs, especially in the development of off-the-shelf products, is increasing. Although the initial receipt of hASCs was relatively limited, there is now greater interest and also awareness that in vitro expansion of hASCs be further explored. The purpose of this study was to assess the integrity of mesenchymal cell characteristics and the mutant capability of chromosome number on hASCs undergoing in vitro expansion. Methods: In this study, three hASC samples from three Vietnamese people were collected and proliferated in MSCCult medium (Regemedlab, Ho Chi Minh City, Viet Nam) to the 5th cell passage. Next, hASCs were evaluated for change of mesenchymal stem cells (MSCs) characteristics including shape, immunophenotype (CD14, CD34, CD44, CD73, CD90, and/or CD166), and trilineage differentiation ability. Finally, the number of chromosomes after passages 1, 3, and 5 was evaluated by karyotyping technique. Results: The results showed that after five passages of culture, hASCs preserved the characteristic shape of MSCs, high expression of mesenchymal markers (e.g. CD44, CD73, CD90, and CD166). However, the cells also maintained their differentiation capacity to develop into various tissues such as bone, cartilage, and fat. The hASCs showed no mutation in the number of chromosomes. However, markers of hematopoietic cells (such as CD14 and CD34) exhibited heterogeneous changes between the samples during proliferation. Conclusion: In conclusion, at passage 5, hASCs retained the integrity of MSC features and there was no mutation discovered in the number of chromosomes. However, further evaluation is needed to conclude that the use of cultured cells in treatment is effective and safe.

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Stem Cell Therapy and Regenerative Medicine

Cited by 35 publications

References 16 publications

Regenerative medicine: Current therapies and future directions

Regenerative medicine: Current therapies and future directions

Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy

Phenotypic and cytogenetic characterization of expanded adipose derived stem cells

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